CBL encodes a protein with negative regulatory activity in protein tyrosine kinase-mediated signaling pathways; CBL may inhibit cell growth resulting from activation of the EGF, PDGF and CSF1 receptors by marking these receptors for ubiquitination and subsequent degradation.
Germinal alterations: the fragile site FRA11B has been localized to a stretch of CCG trinucleotides found in the 5' part of the CBL gene and has been involved in the pathogenesis of a proportion of inherited Jacobsen syndroms which have a del(11)(q23qter) telomeric of an expansion of the stretch of CCG triplets
Sporadic alteration: an extension of an ATG trinucleotide repeat with no translation shift was detected in the coding region of CBL in 9% of the genetically unstable sporadic gastrointestinal tumors,
Somatic mutations have been found in some haematopoietic/lymphoid tissue and lung cancers. Most mutations are “substitution missense” and are related to a protein region located between amino acids 360 and 460.
References (open access):
Cbl and human myeloid neoplasms: the Cbl oncogene comes of age. Kales SC, Ryan PE, Nau MM, Lipkowitz S. Cancer Res. 2010 Jun 15;70(12):4789-94.
Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders. Naramura M, Nadeau S, Mohapatra B, Ahmad G, Mukhopadhyay C, Sattler M, Raja SM, Natarajan A, Band V, Band H. Oncotarget. 2011 Mar;2(3):245-50.
CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases. Tan YH, Krishnaswamy S, Nandi S, Kanteti R, Vora S, Onel K, Hasina R, Lo FY, El-Hashani E, Cervantes G, Robinson M, Hsu HS, Kales SC, Lipkowitz S, Karrison T, Sattler M, Vokes EE, Wang YC, Salgia R. PLoS One. 2010 Jan 29;5(1):e8972.